Postantibiotic and post-beta-lactamase inhibitor effects of amoxicillin plus clavulanate

Antimicrob Agents Chemother. 1996 Dec;40(12):2796-801. doi: 10.1128/AAC.40.12.2796.


The postantibiotic effect (PAE) of amoxicillin-clavulanate was studied for strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, and Escherichia coli. A PAE of approximately 2 h was seen for beta-lactamase-positive and -negative strains of S. aureus following 2 h of exposure to twice the MIC and did not increase at 16 times the MIC. The PAE observed with H. influenzae was clearly related to the growth rate of the organism. A PAE of 0.8 h was found for amoxicillin (four times the MIC) against a beta-lactamase-negative strain of H. influenzae (generation time, 26.3 min) and a PAE of 1.74 h was found for amoxicillin-clavulanate (twice the MIC) against a beta-lactamase-positive strain (generation time, 32.2 min). When the beta-lactamase-positive strain was growing more slowly (generation time, 120 min), the PAE of amoxicillin-clavulanate increased to > 3.32 h. The PAE of amoxicillin-clavulanate at 2/1 micrograms/ml on a beta-lactamase-producing strain of M. catarrhalis was > 2.9 h, and, as expected, the PAEs of twice the MIC on K. pneumoniae and E. coli were generally short (< 1 h). The post-beta-lactamase inhibitor effect (PLIE), determined after removal of only clavulanate, was also examined for beta-lactamase-positive strains. This was more prolonged (approximately 3 to 4 h) than the corresponding PAE for S. aureus, H. influenzae, and M. catarrhalis. The PLIE was related to the amount of beta-lactamase produced and required the presence of amoxicillin in the initial exposure period. These data may have implications for reducing the dosage of amoxicillin-clavulanate.

MeSH terms

  • Amoxicillin / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Clavulanic Acid
  • Clavulanic Acids / pharmacology*
  • Drug Therapy, Combination / pharmacology*
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / enzymology
  • Microbial Sensitivity Tests
  • Moraxella catarrhalis / drug effects
  • Moraxella catarrhalis / enzymology
  • Penicillins / pharmacology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology
  • beta-Lactamase Inhibitors*


  • Anti-Bacterial Agents
  • Clavulanic Acids
  • Penicillins
  • beta-Lactamase Inhibitors
  • Clavulanic Acid
  • Amoxicillin